Rapamycin (also known as sirolimus and marketed under the trade name Rapamune®) is a known macrolide with potent immunosuppressive properties. It also possesses anti-fungal, anti-tumor and anti-inflammatory properties. Rapamycin binds to a member of the FK binding protein (FKBP) family. The rapamycin/FKBP complex binds to the protein kinase mTOR. This binding to mTOR blocks activation of signal transduction pathways and causes arrest of the cell cycle in the G1 phase.
The mTOR signaling network plays a central role in cell survival and proliferation. The network includes multiple players, including PTEN, LKB1, TSC1, TSC2, PI3K, Akt, and eIF4E, among others. Rapamycin is thus an ideal agent for targeting many conditions characterized by detrimental cell survival and proliferation.
There is a continuing need to develop products providing increased bioavailability of rapamycin and rapamycin derivatives. In particular, there is a need to develop sustained release formulations of rapamycin and rapamycin derivatives that do not suffer from low bioavailability, poor release kinetics, injection site toxicity, relatively large volume injections and inconveniently short duration of release. This need is especially evident when treating the sensitive tissues of the eye.